tetracycline and Neoplasm-Metastasis

Effective control of a recurrent malignant pleural effusion can greatly improve the quality of life of the cancer patient. At least a dozen different techniques have been advocated for controlling this common complication of malignant disease. The present review collects and examines the clinical results of all techniques designed to treat this problem. The pathophysiology and diagnostic evaluation of the effusion are also discussed. On the basis of comparisons involving effectiveness, morbidity, and convenience, we recommend intrapleurally administered tetracycline with thoracostomy drainage as the technique of choice. Instillation of a talc suspension with thoracostomy drainage is also a safe and effective technique and should be employed when tetracycline fails or is contraindicated.

Topics: Drainage; Humans; Intubation; Neoplasm Metastasis; Neoplasms; Nitrogen Mustard Compounds; Pleura; Pleural Effusion; Quinacrine; Radioisotopes; Talc; Tetracycline; Thorax

Topics: Fluorescence; Humans; Neoplasm Metastasis; Neoplasms; Stomach Neoplasms; Tetracycline

Although ginseng and related herbs have a long history of utility for various health benefits, their application in cancer therapy and underlying mechanisms of action are not fully understood. Our recent work has shown that 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol (25-OCH(3)-PPD), a newly identified ginsenoside from Panax notoginseng, exerts activities against a variety of cancer cells in vitro and in vivo. This study was designed to investigate its anti-breast cancer activity and the underlying mechanisms of action. We observed that 25-OCH(3)-PPD decreased the survival of breast cancer cells by induction of apoptosis and G1 phase arrest and inhibited the growth of breast cancer xenografts in vivo. We further demonstrated that, in a dose- and time-dependent manner, 25-OCH(3)-PPD inhibited MDM2 expression at both transcriptional and post-translational levels in human breast cancer cells with various p53 statuses (wild type and mutant). Moreover, 25-OCH(3)-PPD inhibited in vitro cell migration, reduced the expression of epithelial-to-mesenchymal transition (EMT) markers, and prevented in vivo metastasis of breast cancer. In summary, 25-OCH(3)-PPD is a potential therapeutic and anti-metastatic agent for human breast cancer through down-regulating MDM2. Further preclinical and clinical development of this agent is warranted.

Topics: Animals; Antineoplastic Agents; Biological Products; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Dose-Response Relationship, Drug; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Ginsenosides; Humans; Mice; Mice, Nude; Neoplasm Metastasis; Protein Stability; Proto-Oncogene Proteins c-mdm2; Tetracycline; Time Factors; Transcription, Genetic; Xenograft Model Antitumor Assays

Although the connexin32 (Cx32)-mediated gap junction is abolished in hepatocellular carcinoma (HCC), the expression of cytoplasmic Cx32 tends to increase in correspondence with the grade of malignancy. Establishing a Tet-off expression system in human nonmetastatic HuH7 HCC cells where cytoplasmic Cx32 was overexpressed by doxycycline (Dox) withdrawal, we previously demonstrated that overexpression of cytoplasmic Cx32 made HuH7 cells metastatic in mice. In our study, hypothesizing that the cytoplasmic Cx32-induced metastasis may involve expansion of the cancer stem cell (CSC) population, we examined whether cytoplasmic Cx32 controlled the size of the side population (SP) in HuH7 Tet-off Cx32 cells. Fluorescence-activated cell sorting revealed that SP was expanded in a Dox-free medium compared with a Dox-supplemented one. Although cytoplasmic Cx32 did not block maturation from SP to non-SP, purified SP reconstituted a larger SP fraction in the Dox-free medium than in the Dox-supplemented one. Furthermore, although SP from HuH7 Tet-off mock cells formed a similar number of CSC spheres of a similar size whether with or without Dox, SP from HuH7 Tet-off Cx32 cells developed a greater number of larger CSC spheres in the Dox-free medium than in the Dox-supplemented one. Taken together, these results suggest that accumulation of cytoplasmic Cx32 should enhance self-renewal of CSC to expand the CSC population in HCC.

Topics: Animals; Anti-Bacterial Agents; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Connexins; Cytoplasm; Doxycycline; Flow Cytometry; Fluorescent Antibody Technique, Indirect; Gap Junction beta-1 Protein; Gene Expression; Humans; Immunoblotting; Liver Neoplasms, Experimental; Male; Mice; Mice, SCID; Neoplasm Metastasis; Neoplastic Stem Cells; Tetracycline; Transplantation, Heterologous

To investigate the correlation between matrix metalloproteinase 9 (MMP-9) expression and tumor invasion and metastasis as well, and to explore the potential application of controlled expression of target gene in tumor gene therapy.. One self-contained tetracycline-regulated retroviral vector containing anti-sense cDNA of MMP-9 was constructed and transfected into a metastatic human melanoma cell line WM451 which expressed a high level of MMP-9. Techniques such as growth rate measurment, MTT assay, (3)H-thymidine incorporation, colony forming ability in soft agar, invasion assay in Boyden chamber, as well as zymography and Western blot were applied to analyze the expression of MMPs and behaviors of tumor cells in vitro before and after gene transfection. Tumorigenecity and spontaneous metastasis were tested in nude mice.. In the presence of exogenous tetracycline, the transfected antisense MMP-9 did not affect the endogenous level of MMP-9 in WM451 cells, and showed no significant changes in cell behaviors in comparison with that of the vector-transfected control cells. Nevertheless, withdrawal of tetracycline from the medium caused a significant down-regulation of expression and activity of MMP-9. The capacity of cell growth in vitro, colony forming ability in soft agar, invasion through Matrigel all were inhibited remarkably when compared with the controls. Spontaneous metastasis in nude mice was significantly inhibited.. Transfection of anti-sense MMP-9 can down-regulate the invasion and metastasis of melanoma cells both in vitro and in vivo, further clarifying the important role of MMP-9 in tumor progression.

Topics: Animals; Cell Division; Cell Line, Tumor; DNA, Antisense; DNA, Complementary; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; Genetic Vectors; Humans; Matrix Metalloproteinase 9; Melanoma; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Transplantation; Retroviridae; Tetracycline; Transfection

We describe an approach employing intramuscular plasmid electrotransfer to deliver secretable forms of K1-5 and K1-3-HSA (a fusion of K1-3 with human serum albumin), which span, respectively, five and three of the five kringle domains of plasminogen. A tetracycline-inducible system (Tet-On) composed of three plasmids coding, respectively, for the transgene, the tetracycline transcriptional activator rtTA, and the silencer tTS was employed. K1-3-HSA and K1-5, produced from C2C12 muscle cells, were found to inhibit endothelial cell (HMEC-1) proliferation by 30 and 51%, respectively. In vivo, the expression of the transgene upon doxycycline stimulation was rapid, stable, and tightly regulated (no background expression) and could be maintained for at least 3 months. Blood half-lives of 2.1 and 3.7 days were found for K1-5 and K1-3-HSA, respectively. The K1-5 protein was secreted from muscle into blood at a level of 45 ng/ml, which was sufficient to inhibit MDA-MB-231 tumor growth by 81% in nude mice and B16-F10 melanoma cell lung invasion in C57BL/6 mice by 73%. PECAM-1 immunostaining studies revealed modest tumor vasculature in mice expressing K1-5. In contrast, K1-3-HSA, although secreted into blood at much higher level (250 ng/ml) than K1-5, had no effect on tumor growth.

Topics: Angiogenesis Inhibitors; Electroporation; Gene Expression Regulation; Genetic Vectors; Muscle, Skeletal; Neoplasm Metastasis; Neoplasms; Peptides; Plasmids; Plasminogen; Tetracycline; Time Factors

The molecular mechanisms leading to prostate cancer remain poorly understood, especially concerning the progression to the metastatic form. SSeCKS, a major protein kinase C substrate with tumor suppressor activity, is likely the rodent orthologue of human Gravin/AKAP12, a scaffolding protein for protein kinases A and C. Gravin was mapped as a single-copy gene to 6q24-25.2, a hotspot for deletion in advanced prostate cancer, and therefore, we investigated the role of SSeCKS/Gravin in prostate oncogenesis. SSeCKS/Gravin protein was detected in untransformed rat and human prostate epithelial cell lines EP12 and PZ-HPV-7, respectively, and in human prostatic epithelium, especially basal epithelial cells. In contrast, SSeCKS/Gravin protein and RNA levels were severely reduced in human (PC-3, PPC-1, LNCaP, DU145, and TSU) and rat Dunning (AT3.1 and MatLyLu) prostate cancer cell lines. The regulated reexpression of SSeCKS in MatLyLu cells induced filopodia-like projections and a decrease in anchorage-independent growth. In nude mice, SSeCKS reexpression slightly decreased primary-site tumor growth but severely decreased the formation of lung metastases. Primary-site tumors that progressed lost regulated SSeCKS reexpression. SSeCKS/Gravin expression was detected in benign human prostatic lesions and well-differentiated carcinomas but not in undifferentiated lesions with Gleason sums > or =6. Our data suggest a role for the loss of SSeCKS/Gravin in the metastatic progression of human prostate cancer.

Topics: A Kinase Anchor Proteins; Animals; Biomarkers, Tumor; Cell Cycle Proteins; Cell Differentiation; Cell Division; Chromosome Banding; Chromosome Mapping; Chromosomes, Human, Pair 6; Female; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; In Situ Hybridization, Fluorescence; Male; Mice; Mice, Nude; Mitogens; Molecular Weight; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms, Experimental; Prostatic Neoplasms; Protein Isoforms; Proteins; Rats; RNA, Neoplasm; Tetracycline; Transplantation, Heterologous; Tumor Cells, Cultured

Neutral endopeptidase 24.11 (NEP) is a cell-surface enzyme expressed by prostatic epithelial cells that cleaves and inactivates neuropeptides implicated in the growth of androgen-independent prostate cancer (PC). We report that NEP expression and catalytic activity are lost in vitro in androgen-independent but not androgen-dependent PC cell lines. In vivo, NEP protein expression is commonly decreased in cancer cells of metastatic PC specimens from patients with androgen-independent but not androgen-dependent PC. Overexpression of NEP in androgen-independent PC cells or incubation with recombinant NEP inhibits PC cell growth. Furthermore, in androgen-dependent PC cells, expression of NEP is transcriptionally regulated by androgen and decreases with androgen withdrawal. These data suggest that decreased NEP expression, common in androgen-independent PCs, is facilitated by the elimination of androgens, and that NEP loss plays an important role in the development of androgen-independent PC by allowing PC cells to use mitogenic neuropeptides as an alternate source to androgen in order to stimulate cell proliferation.

Topics: Biomarkers, Tumor; Biopsy; Cell Division; Cell Nucleus; Dihydrotestosterone; Disease Progression; Gene Transfer Techniques; Humans; Kinetics; Male; Neoplasm Metastasis; Neprilysin; Polymerase Chain Reaction; Prostatic Neoplasms; Recombinant Proteins; Tetracycline; Time Factors; Transfection; Tumor Cells, Cultured

We report our experience in the treatment of pleural effusion in 25 patients with metastatic breast cancer. Seventeen patients received initial systemic therapy and in 13 of them local intrapleural therapy was subsequently employed; the remaining 8 patients received local therapy only. Several modalities of local treatment were used: intrapleural chemotherapy with thiotepa and 5-fluorouracil; the production of pleural adhesion by the use of chest drainage alone or associated with instillation of sclerosing agents, such as nitrogen mustard or tetracycline. Of the 21 patients who were subjected to local therapy, 19 (90.5%) achieved an objective response (16 complete (76.2%) and 3 (14.34%) partial). Complete responses were observed exclusively in patients who had pleurodesis. Our data suggest that pleurodesis is the treatment of choice for neoplastic pleural effusion and that the use of tetracycline as a sclerosing agent is the most useful because of its availability, low cost and low morbidity.

Topics: Adult; Aged; Breast Neoplasms; Female; Humans; Middle Aged; Neoplasm Metastasis; Pleural Effusion; Sclerosing Solutions; Tetracycline

We have previously reported the development of an extensive invasive growth of the thyroid gland of the gynogenetic teleost, Poecilia formosa (the Amazon molly), following i.p. injection of UV- or gamma-irradiated thyroid cells. This result was surprising by comparison with mammalian work, in which the thyroid is rarely the site for tumor metastases, but the anatomy of the circulation of fish is different from mammals, and in fish the gills and thyroid gland would be among the first tissues in which injected cells might be arrested. Techniques using a fluorescent dye, 125I membrane label, or [3H]thymidine label were used to follow the distribution of i.p. injected cells in the Amazon molly. Fish sampled as soon as 30 min after injection had some labeled cells dispersed in the connective tissue around the ventral aorta and in the bases of the gills, and by 1 to 4 hr large numbers of cells had moved into the thyroid region. A few cells still persisted there 200 hr later. Experiments on the distribution of heat-killed cells indicated that the initial distribution of the cells was largely governed by mechanical factors. Injected cells would appear to be disseminated in fish by mechanisms similar to those in mammals.

Topics: Animals; Autoradiography; Cell Movement; Fishes; Injections, Intraperitoneal; Methods; Neoplasm Metastasis; Sulfanilic Acids; Tetracycline; Thymidine; Thyroid Gland

Salmonella empyema in an immunologically compromised patient with malignant pleural effusion is described. Antimicrobial treatment was ineffective when given parenterally. Intrapleural administration of antibiotics resulted in a rapid rise of the antibacterial activity of the pleural fluid, leading to rapid clinical improvement and eradication of the infections.

Topics: Adenocarcinoma; Empyema; Humans; Lung Neoplasms; Male; Microbial Sensitivity Tests; Middle Aged; Neoplasm Metastasis; Pleural Effusion; Salmonella; Salmonella Infections; Tetracycline; Thyroid Neoplasms

Tumor-seeking radiopharmaceuticals have been employed in the diagnosis of primary neoplasms, in the detection of distant disease, particularly in the localization of tumor foci to facilitate biopsies and the planning of radiation portals, and in assessing the response to tumor therapy. At the present, there is no ideal tumor-scanning agent. However, several approaches appear to be useful and offer promise for further study. The greatest experience has been with Gallium-67, which has major utility in the staging of Hodgkin's disease, in the diagnosis of bronchogenic carcinoma, in the detection of certain metastatic brain tumors, in the identification of recurrent disease, and in the noninvasive diagnosis of leukemic complications. A number of radiolabeled antibiotic and chemotherapeutic agents have shown promise, including tetracycline and bleomycin. A major drawback, however, of these agents which is shared with Gallium-67 is that they appear to be sequestered by inflammatory as well as neoplastic tissue. A most intriguing approach is the use of radiolabeled antibodies to tumor-associated antigens. Animal and clinical experiments have employed antifibrin, antifibrinogen, anticarcinoembryonic antigen, and antiferritin. Theoretically, agents such as these should allow for greater tumor specificity.

Topics: Antibodies, Neoplasm; Bleomycin; Brain Neoplasms; Carcinoembryonic Antigen; Carcinoma, Bronchogenic; Gallium Radioisotopes; Hodgkin Disease; Humans; Indium; Leukemia; Lung Neoplasms; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasms; Radiography; Radioisotopes; Radionuclide Imaging; Technetium; Tetracycline

A prospective study of 40 consecutive classic primary osteosarcomas employing tomography, angiography, radio-scanning, tetracycline labelling, macroscopic and microscopic study revealed that in 10 (25%) "skip" metastases were found. In 8 the "skips" were completely unsuspected prior to computation. It is evident that patients with "skips" are more prone to local recurrence and have a worse prognosis following amputation than those without such satellite lesions. Through-bone amputation entails a considered risk of leaving micro-foci of tumor; proximal disarticulation does not obviate the risk of cross joint "skips" when the lesion is in a sub-articular site. What affect such residual foci has upon the effectiveness of adjunct therapy and conversely whether such therapy will permit more conservative surgery by suppressing residual "skips" is an important but unanswered question.

Topics: Adolescent; Adult; Aged; Amputation, Surgical; Bone Neoplasms; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Osteosarcoma; Prospective Studies; Tetracycline

Topics: Adenocarcinoma; Animals; Carcinoma, Bronchogenic; Carcinoma, Hepatocellular; Gallium; Glioblastoma; Hodgkin Disease; Humans; L-Lactate Dehydrogenase; Liver Neoplasms; Lung Neoplasms; Mediastinal Neoplasms; Methane; Mice; Muscular Diseases; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms, Experimental; Nitrosourea Compounds; Osteosarcoma; Rabbits; Radioisotopes; Radionuclide Imaging; Rats; Sarcoma; Sarcoma, Experimental; Technetium; Tetracycline; Transplantation, Homologous

Topics: Carcinoma, Bronchogenic; Carcinoma, Small Cell; Cyclophosphamide; Humans; Lung Neoplasms; Neoplasm Metastasis; Tetracycline; Time Factors

Topics: Adolescent; Adult; Animals; Antigens, Neoplasm; Blood Proteins; Bone Neoplasms; Child; Child, Preschool; Epitopes; Female; Femoral Neoplasms; Fluoresceins; Humans; Immune Sera; Immunity, Active; Immunity, Maternally-Acquired; Immunization, Passive; Immunodiffusion; Immunoelectrophoresis; Immunotherapy; Infant; Leukocyte Count; Lung Neoplasms; Lymphocyte Activation; Lymphocytes; Male; Neoplasm Metastasis; Neoplasm Transplantation; Osteosarcoma; Rabbits; Skin Tests; Tetracycline; Tibia

Topics: Administration, Oral; Adult; Aged; Biopsy; Carcinoma, Adenoid Cystic; Carcinoma, Squamous Cell; Female; Fluorescence; Humans; Injections, Intravenous; Laryngeal Neoplasms; Leukoplakia; Lymphoma; Male; Methods; Middle Aged; Mouth Neoplasms; Neoplasm Metastasis; Pharyngeal Neoplasms; Tetracycline; Time Factors

Topics: Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Breast Neoplasms; Carcinoma; Drug Synergism; Female; Humans; Leukemia, Myeloid, Acute; Lung; Male; Middle Aged; Neoplasm Metastasis; Ovarian Neoplasms; Prednisone; Radiography; Remission, Spontaneous; Sarcoma; Tetracycline; Vincristine

Topics: Abdominal Neoplasms; Adolescent; Adult; Aged; Drainage; Evaluation Studies as Topic; Female; Gastrointestinal Neoplasms; Genital Neoplasms, Female; Humans; Injections, Intravenous; Laparotomy; Middle Aged; Neoplasm Metastasis; Surgical Wound Infection; Suture Techniques; Sutures; Tetracycline; Wound Healing

Topics: Adult; Aged; Breast Neoplasms; Evaluation Studies as Topic; Female; Follow-Up Studies; Humans; Kidney Neoplasms; Lung Neoplasms; Male; Methods; Middle Aged; Neoplasm Metastasis; Pleural Effusion; Radiography, Thoracic; Tetracycline

Topics: Adult; Bone Neoplasms; Cervical Vertebrae; Cobalt Isotopes; Cyclophosphamide; Humans; Lung Neoplasms; Male; Metacarpus; Neoplasm Metastasis; Nose Neoplasms; Petrous Bone; Radiography; Sarcoma, Ewing; Skull Neoplasms; Tetracycline; Thoracic Vertebrae

Topics: Adult; Aged; Eyelids; Head; Humans; Lip Neoplasms; Male; Middle Aged; Neck; Neoplasm Metastasis; Skin Neoplasms; Sulfuric Acids; Surgical Wound Infection; Tetracycline; Thorax

Topics: Adult; Aged; Diagnosis, Differential; Female; Humans; Male; Mediastinal Neoplasms; Neoplasm Metastasis; Neoplasm Recurrence, Local; Osteochondritis; Radiography; Radiotherapy; Ribs; Sternoclavicular Joint; Tetracycline; Tomography

Topics: Colonic Neoplasms; Colostomy; Drug Therapy; Humans; Ileostomy; Kanamycin; Neomycin; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasms; Postoperative Complications; Preoperative Care; Rectal Neoplasms; Rectum; Sulfonamides; Surgical Procedures, Operative; Sutures; Tetracycline